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A Study to Evaluate Efficacy, Safety, and Tolerability of EID of Natalizumab (BG00002) in Participants With RRMS Switching From Treatment With Natalizumab SID in Relation to Continued SID Treatment- Followed by Extension Study Comprising SC and IV Natalizumab Administration

Sponsor
Biogen (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03689972
Collaborator
(none)
500
Enrollment
97
Locations
4
Arms
49.7
Anticipated Duration (Months)
5.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Part 1: The primary objective is to evaluate the efficacy of natalizumab extended interval dosing (EID) in participants who have previously been treated with natalizumab standard interval dosing (SID) for at least 12 months, in relation to continued SID treatment. The secondary objectives is to evaluate relapse-based clinical efficacy measures, disability worsening, additional Magnetic resonance imaging (MRI)-lesion efficacy measures and safety of EID in participants who have previously been treated with natalizumab SID for at least 12 months, in relation to continued SID treatment.

Part 2: The primary objective is to evaluate participant preference for subcutaneous (SC) versus intravenous (IV) route of natalizumab administration. The secondary objectives is to evaluate treatment satisfaction, drug preparation and administration time, safety and immunogenicity, efficacy and characterize pharmacokinetic (PK) and pharmacodynamic (PD) drug preparation and administration time of SC versus IV routes of natalizumab administration.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This study will be conducted in 2 parts. At the end of part 1, participants who provide consent and are eligible, and newly enrolled participants, will enter part 2, an Open Label Extension comprising a crossover analysis.

Those participants who completed part 1 and cannot participate, or elect not to participate, in Part 2 (Open label extension) will enter a 12-week follow-up.

Study Design

Study Type:
Interventional
Actual Enrollment :
500 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Controlled, Open-Label, Rater-Blinded, Phase 3b Study of the Efficacy, Safety, and Tolerability of 6-Week Extended Interval Dosing (EID) of Natalizumab (BG00002) in Subjects With Relapsing-Remitting Multiple Sclerosis Switching From Treatment With 4-Week Natalizumab Standard Interval Dosing (SID) in Relation to Continued SID Treatment - Followed by an Open-Label Crossover Extension Study Comprising Subcutaneous and Intravenous Natalizumab Administration
Actual Study Start Date :
Dec 26, 2018
Anticipated Primary Completion Date :
Aug 31, 2022
Anticipated Study Completion Date :
Feb 15, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1: Standard Interval Dosing (SID) IV

Participants will receive natalizumab 300 milligram (mg) intravenous (IV) infusion every 4 weeks (-2/+5 days) up to Week 72.

Drug: Natalizumab
Natalizumab 300 mg SC injection or IV infusion.
Other Names:
  • BG00002

    		•
    Experimental: Part 1: Extended Interval Dosing (EID) IV

    Participants will receive natalizumab 300 mg IV infusion every 6 weeks (-2/+5 days) up to Week 72.

    Drug: Natalizumab
    Natalizumab 300 mg SC injection or IV infusion.
    Other Names:
  • BG00002

    		•
    Experimental: Part 2: EID SC, then EID IV

    Participants will receive natalizumab 300 mg SC injection every 6 weeks from Week 108 through Week 126 followed by natalizumab 300 mg IV infusion every 6 weeks from Week 132 through Week 150.

    Drug: Natalizumab
    Natalizumab 300 mg SC injection or IV infusion.
    Other Names:
  • BG00002

    		•
    Experimental: Part 2: EID IV, then EID SC

    Participants will receive natalizumab 300 mg IV infusion every 6 weeks from Week 108 through Week 126 followed by natalizumab 300 mg SC injection every 6 weeks from Week 132 through Week 150.

    Drug: Natalizumab
    Natalizumab 300 mg SC injection or IV infusion.
    Other Names:
  • BG00002

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Part 1: Number of New or Newly Enlarging T2 Hyperintense Lesions at Week 72 [Week 72]

      Number of new or newly enlarging T2 hyperintense lesions will be analysed by magnetic resonance imaging (MRI) scans of brain. New MRI scans will be compared with the prior MRI scans to analyse the number of new or newly enlarging T2 hyperintense lesions.

    2. Part 2: Percentage of Participants Indicating a Preference for Natalizumab SC Administration at the End of Part 2 [Week 156]

    Secondary Outcome Measures

    1. Part1: Time to First Relapse as Adjudicated by an Independent Neurology Evaluation Committee (INEC) [Up to Week 72]

      A multiple sclerosis (MS) relapse will be defined as the onset of new or recurrent neurological symptoms, not associated with fever, infection, severe stress, or drug toxicity, lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination. Only relapses confirmed by an INEC will be included in the analysis.

    2. Part 1: Number of New Gadolinium (Gd) Enhancing and New T1 Hypointense Lesions at Weeks 24, 48 and 72 [Weeks 24, 48 and 72]

      Number of new Gd enhancing and new T1 hypointense lesions on brain will be analysed by MRI scans of brain. New MRI scans will be compared with the prior MRI scans to analyse number of new Gd enhancing and new T1 hypointense lesions.

    3. Part 1: Annualized Relapse Rate at Week 72 [Week 72]

      An MS relapse will be defined as the onset of new or recurrent neurological symptoms, not associated with fever, infection, severe stress, or drug toxicity, lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination. Only relapses confirmed by an INEC will be included in the analysis.

    4. Part 1: Number of New or Newly Enlarging T2 Hyperintense Lesions at Weeks 24 and 48 [Weeks 24 and 48]

      Number of new or newly enlarging T2 hyperintense lesions will be analysed by MRI scans of brain. New MRI scans will be compared with the prior MRI scans to analyse the number of new or newly enlarging T2 hyperintense lesions.

    5. Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to Week 96]

      An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, is a medically important event.

    6. Part 1: Time to Expanded Disability Status Scale (EDSS) Worsening as Confirmed After at Least 24 Weeks [Week 24, 48, 72 and 84]

      Confirmed EDSS worsening is defined as an increase of at least 1.0 point from a baseline EDSS score ≥ 1.0 or an increase of at least 1.5 points from a baseline EDSS score of 0 that is confirmed after at least 24 weeks.

    7. Part 2: Total Score on Treatment Satisfaction Questionnaire for Medication (TSQM) [Up to Week 156]

      The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience using transformed scores between 0 and 100 for effectiveness. Higher scores indicates greater satisfaction.

    8. Part 2: Mean Time for Drug Preparation and Administration [Up to Week 156]

    9. Part 2: Number of Participants with Treatment Emergent AEs (TEAEs) [From Week 132 to Week 156]

      An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is any event in participants who had received at least 1 dose of study drug, regardless of relationship to study drug.

    10. Part 2: Percentage of Participants With Anti-Natalizumab Antibodies [From Week 132 to Week 156]

    11. Part 2: Number of New or Newly Enlarging T2 Hyperintense Lesions [From Week 132 to Week 156]

      Number of new or newly enlarging T2 hyperintense lesions will be analysed by magnetic resonance imaging (MRI) scans of brain. New MRI scans will be compared with the prior MRI scans to analyse the number of new or newly enlarging T2 hyperintense lesions.

    12. Part 2: Time to First Relapse [From Week 132 to Week 156]

      A MS relapse will be defined as the onset of new or recurrent neurological symptoms, not associated with fever, infection, severe stress, or drug toxicity, lasting at least 24 hours.

    13. Part 2: Annualized Relapse Rate [From Week 132 to Week 156]

      Annualized relapse rate included relapses reported prior to the end of each period.

    14. Part 2: Change in Expanded Disability Status Scale (EDSS) Score [From Week 132 to Week 156]

      The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability.

    15. Part 2: Number of New Gadolinium (Gd) Enhancing Lesions [From Week 132 to Week 156]

      Number of new Gd enhancing lesions on brain will be analysed by MRI scans of brain. New MRI scans will be compared with the prior MRI scans to analyse number of new Gd enhancing lesions.

    16. Part 2: Number of New T1 Hypointense Lesions [From Week 132 to Week 156]

      Number of new T1 hypointense lesions on brain will be analysed by MRI scans of brain. New MRI scans will be compared with the prior MRI scans to analyse number new T1 hypointense lesions.

    17. Part 2: Percentage of Brain Volume Change [From Week 132 to Week 156]

    18. Part 2: Change in Cortical and Thalamic Brain Region Volume [From Week 132 to Week 156]

    19. Part 2: Trough Serum Concentration of Natalizumab (Ctrough) [From Week 132 to Week 156]

    20. Part 2: Trough α4 Integrin Saturation [From Week 132 to Week 156]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:
    For Part 1:

    • Ability of the participant to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations.

    • Diagnosis of relapsing remitting multiple sclerosis (RRMS) according to the McDonald criteria [Thompson 2018].

    • Treatment with natalizumab as disease-modifying monotherapy for RRMS that is consistent with the approved dosing for a minimum of 12 months prior to randomization. The participant must have received at least 11 doses of natalizumab in the 12 months prior to randomization with no missed doses in the 3 months prior to randomization.

    • Expanded Disability Status Scale (EDSS) score <=5.5 at screening.

    • No relapses in the last 12 months prior to randomization, as determined by the enrolling Investigator.

    For Part 2:

    • Ability of the participants to understand the purpose and risks of the study and provide signed and dated informed consent for Part 2 and authorization to use confidential health information in accordance with national and local participant privacy regulations.

    • Completed Part 1 Week 72 visit while remaining on their randomized treatment assignment of SID or EID.

    Key Exclusion Criteria:
    For Part 1:

    • Primary and secondary progressive multiple sclerosis (MS).

    • MRI positive for Gd-enhancing lesions at screening.

    • Participants for whom MRI is contraindicated (e.g., have a contraindicated pacemaker or other contraindicated implanted metal device, have suffered, or are at risk for, side effects from Gd, or have claustrophobia that cannot be medically managed).

    • History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic (including diabetes), urologic, pulmonary, neurologic (except for RRMS), dermatologic, psychiatric, renal, or other major disease that would preclude participation in a clinical study, in the opinion of the Investigator.

    • Presence of anti-natalizumab antibodies at screening.

    For Part 2:

    • Participants treated with natalizumab EID was reverted to natalizumab SID by choice or as rescue treatment in Part 1.

    • Participant received treatment with any MS disease-modifying therapy other than natalizumab in Part 1 or in the period between Part 1 and Part 2.

    • History of human immunodeficiency virus or history of other immunodeficient conditions.

    • Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 30 days (or 5 half-lives of the agent, whichever is longer) prior to the Baseline Visit or at any time during this study.

    • Inability to comply with study requirements.

    • Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the participant unsuitable for enrollment.

    The inclusion and exclusion criteria for new participants who did not participate in Part 1 of the study are the same as those for participants who did participate in Part 1.

    NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Cullman Alabama United States 35058
    2 Research Site Homewood Alabama United States 35209
    3 Research Site Irvine California United States 92697
    4 Research Site La Jolla California United States 92037
    5 Research Site Newport Beach California United States 92663
    6 Research Site Palo Alto California United States 94304
    7 Research Site Aurora Colorado United States 80045
    8 Research Site Fort Collins Colorado United States 80528
    9 Research Site Fairfield Connecticut United States 06824
    10 Research Site Miami Florida United States 33136
    11 Research Site Sunrise Florida United States 33351
    12 Research Site Tampa Florida United States 33612
    13 Research Site Atlanta Georgia United States 30309
    14 Research Site Atlanta Georgia United States 30327
    15 Research Site Chicago Illinois United States 60611
    16 Research Site Glenview Illinois United States 60026
    17 Research Site Overland Park Kansas United States 66212
    18 Research Site Boston Massachusetts United States 02215
    19 Research Site Foxboro Massachusetts United States 02035
    20 Research Site Lexington Massachusetts United States 02421
    21 Research Site Wellesley Massachusetts United States 02481
    22 Research Site Farmington Hills Michigan United States 48334
    23 Research Site Owosso Michigan United States 48867
    24 Research Site Golden Valley Minnesota United States 55422
    25 Research Site Saint Louis Missouri United States 63110
    26 Research Site Las Vegas Nevada United States 89101
    27 Research Site Livingston New Jersey United States 07039
    28 Research Site Teaneck New Jersey United States 07666
    29 Research Site New York New York United States 10016
    30 Research Site New York New York United States 10029
    31 Research Site New York New York United States 10032
    32 Research Site Patchogue New York United States 11772
    33 Research Site Raleigh North Carolina United States 27607-6010
    34 Research Site Winston-Salem North Carolina United States 27157
    35 Research Site Cleveland Ohio United States 44195
    36 Research Site Dayton Ohio United States 45417
    37 Research Site Dayton Ohio United States 45459
    38 Research Site Portland Oregon United States 97225
    39 Research Site Philadelphia Pennsylvania United States 19107
    40 Research Site Pittsburgh Pennsylvania United States 15213
    41 Research Site Knoxville Tennessee United States 37934
    42 Research Site Nashville Tennessee United States 37215
    43 Research Site Round Rock Texas United States 78681
    44 Research Site Salt Lake City Utah United States 84103
    45 Research Site Charlottesville Virginia United States 22903
    46 Research Site Vienna Virginia United States 22182
    47 Research Site Seattle Washington United States 98101
    48 Research Site Milwaukee Wisconsin United States 53215
    49 Research Site St Leonards New South Wales Australia 2065
    50 Research Site Sydney New South Wales Australia 2050
    51 Research Site Box Hill Victoria Australia 3128
    52 Research Site Melbourne Victoria Australia 3004
    53 Research Site Parkville Victoria Australia 3050
    54 Research Site Bruxelles Belgium 1070
    55 Research Site Bruxelles Belgium 1200
    56 Research Site Edegem Belgium 2650
    57 Research Site La Louvière Belgium 7100
    58 Research Site Toronto Ontario Canada M5B 1W8
    59 Research Site Gatineau Quebec Canada J8Y 1W2
    60 Research Site Greenfield Park Quebec Canada J4V 2J2
    61 Research Site Montreal Quebec Canada H2X 0A9
    62 Research Site Montreal Quebec Canada H3A 3B4
    63 Research Site Bordeaux France 33076
    64 Reseach Site Caen France 14033
    65 Research Site Lille France 59037
    66 Research Site Nice France 06002
    67 Research Site Saint Herblain France 44800
    68 Research Site Strasbourg France 67091
    69 Research Site Bamberg Germany 96052
    70 Research Site Berlin Germany 10117
    71 Research Site Bochum Germany 44791
    72 Research Site Erbach Germany 64711
    73 Research Site Essen Germany 45147
    74 Research Site Freiburg Germany 79106
    75 Research Site Marburg Germany 35043
    76 Research Site Muenster Germany 48149
    77 Research Site Munich Germany 81675
    78 Research Site Stuttgart Germany 70182
    79 Research Site Ramat Gan Israel 52363
    80 Research Site Catania Italy 95123
    81 Research Site Cefalù Italy 90015
    82 Research Site Milano Italy 20123
    83 Research Site Napoli Italy 80131
    84 Research Site Pozzilli Italy 86077
    85 Research Site Breda Netherlands 4818 CK
    86 Research Site Nieuwegein Netherlands 3435 CM
    87 Research Site Sittard Netherlands 6162 BG
    88 Research Site Lleida Catalonia Spain 25198
    89 Research Site El Palmar Murcia Spain 30120
    90 Research Site Madrid Spain 28034
    91 Research Site Malaga Spain 29010
    92 Research Site Sevilla Spain 41009
    93 Research Site London United Kingdom W6 8RF
    94 Research Site Nottingham United Kingdom NG7 2UH
    95 Research Site Salford United Kingdom M6 8HD
    96 Research Site Sheffield United Kingdom S10 2JF
    97 Research Site Swansea United Kingdom SA6 6NL

    Sponsors and Collaborators

    • Biogen

    Investigators

    • Study Director: Medical Director, Biogen

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Biogen
    ClinicalTrials.gov Identifier:
    NCT03689972
    Other Study ID Numbers:
    • 101MS329
    • 2018-002145-11
    First Posted:
    Oct 1, 2018
    Last Update Posted:
    Sep 18, 2020
    Last Verified:
    Sep 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Multiple Sclerosis
    Multiple Sclerosis, Relapsing-Remitting
    Sclerosis
    Natalizumab

    Study Results

    No Results Posted as of Sep 18, 2020